探索小分子在抗疟药物武器库中的最新开创性进展:化学视角评估。
Exploring the Recent Pioneering Developments of Small Molecules in Antimalarial Drug Armamentarium: A Chemistry Prospective Appraisal.
机构信息
Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban, 4000, South Africa.
Department of Pharmaceutical Chemistry, SVKM's NMIMS, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, Vile Parle (West), Mumbai, 400056, Maharashtra, India.
出版信息
Chem Biodivers. 2024 Aug;21(8):e202400460. doi: 10.1002/cbdv.202400460. Epub 2024 Jul 3.
Malaria is a very destructive and lethal parasitic disease that causes significant mortality worldwide, resulting in the loss of millions of lives annually. It is an infectious disease transmitted by mosquitoes, which is caused by different species of the parasite protozoan belonging to the genus Plasmodium. The uncontrolled intake of antimalarial drugs often employed in clinical settings has resulted in the emergence of numerous strains of plasmodium that are resistant to these drugs, including multidrug-resistant strains. This resistance significantly diminishes the effectiveness of many primary drugs used in the treatment of malaria. Hence, there is an urgent need for developing unique classes of antimalarial drugs that function with distinct mechanisms of action. In this context, the design and development of hybrid compounds that combine pharmacophoric properties from different lead molecules into a single unit gives a unique perspective towards further development of malaria drugs in the next generation. In recent years, the field of medicinal chemistry has made significant efforts resulting in the discovery and synthesis of numerous small novel compounds that exhibit potent antimalarial properties, while also demonstrating reduced toxicity and desirable efficacy. In light of this, we have reviewed the progress of hybrid antimalarial agents from 2021 up to the present. This manuscript presents a comprehensive overview of the latest advancements in the medicinal chemistry pertaining to small molecules, with a specific focus on their potential as antimalarial agents. As possible antimalarial drugs that might target both the dual stage and multi-stage stages of the parasite life cycle, these small hybrid molecules have been studied. This review explores a variety of physiologically active compounds that have been described in the literature in order to lay a strong foundation for the logical design and eventual identification of antimalarial drugs based on lead frameworks.
疟疾是一种极具破坏性和致命性的寄生虫病,在全球范围内造成了大量的死亡,每年导致数百万人失去生命。它是一种由蚊子传播的传染病,由属于疟原虫属的不同种寄生虫引起。临床中经常使用的抗疟药物的不受控制的摄入导致了许多对这些药物具有抗药性的疟原虫株的出现,包括多药耐药株。这种耐药性大大降低了许多用于治疗疟疾的主要药物的有效性。因此,迫切需要开发具有独特作用机制的抗疟药物。在这种情况下,将来自不同先导分子的药效团特性组合到一个单一单元中的杂合化合物的设计和开发为下一代疟疾药物的进一步发展提供了独特的视角。近年来,药物化学领域做出了巨大努力,发现并合成了许多具有强大抗疟特性的新型小分子化合物,同时还表现出降低的毒性和理想的疗效。有鉴于此,我们回顾了 2021 年至今的杂合抗疟药物的进展。本文全面概述了小分子药物化学方面的最新进展,特别关注它们作为抗疟药物的潜力。这些小分子杂合分子被研究为可能针对寄生虫生命周期的双重阶段和多阶段的潜在抗疟药物。本综述探讨了文献中描述的各种具有生理活性的化合物,为基于先导框架的合理设计和最终鉴定抗疟药物奠定了坚实的基础。